Dr Steve Sweet
|Post:||Senior Research Fellow (Genome Damage and Stability)|
|Location:||Genome Centre G3.05|
|International:||+44 1273 877414|
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[2009-2011] Postdoctoral Researcher, Northwestern University, IL, USA. Professor Neil Kelleher.
I applied dual label stable-isotope labeling (SILAC) to differentiate both new and old histones and new and old methylation. This allowed us to observe the re-establishment of methylation that occurs after DNA replication or co-transcriptionally. Histone PTMs have been suggested to be epigenetic in nature: the ‘inheritance’ of methylation status after cell division is therefore highly relevant. Interestingly, our findings for H3K79 methylation suggested a certain amount of positional ‘scrambling’ occurs.
An additional project analyzed global histone alterations that occur as a result of the multiple myeloma t(4;14) translocation and MMSET methyltransferase over-expression. This is a causative event in multiple myeloma, underscoring the significance of histone modifications.
[2006-2009] Biosciences, University of Birmingham. Dr Helen Cooper and Professor John Heath.
Src-dependent protein interactions and tyrosine phosphorylation in the FGF pathway were identified using SILAC relative quantification. Electron capture dissociation was applied to the on-line identification and site-localization of protein phosphorylation, using both targeted and proteomic approaches. Site-localization software (SLoMo) was developed to analyse the phosphoproteomic dataset.
[2002-2005] Phosphoprotein Analysis by Mass Spectrometry
Department of Chemistry, The University of Manchester. Professor Simon Gaskell.
My PhD focussed on novel method development, including phosphopeptide enrichment using SCX-based diagonal chromatography and TiO2. Novel phosphorylation sites were identified from the TGF-β receptor and quantified using iTRAQ.
[2001-2002] Department of Biochemistry, University of Cambridge. Dr Sarah Lummis.
The ligand specificity of the 5HT3-R was investigated using site-directed mutagenesis, radioligand-binding assays and electrophysiology (patch-clamping).
Principal Investigator in the Genome Damage and Stability Centre.
My career to date has concentrated on the analysis of protein post-translational modifications by mass spectrometry. I intend to apply this skill-set to the problem of DNA damage repair, and the involvement of chromatin therein.
Zheng, Yupeng, Sweet, Steve M M, Popovic, Relja, Martinez-Garcia, Eva, Tipton, Jeremiah D, Thomas, Paul M, Licht, Jonathan D and Kelleher, Neil L (2012) Total kinetic analysis reveals how combinatorial methylation patterns are established on lysines 27 and 36 of histone H3. Proceedings of the National Academy of Sciences of the United States of America (PNAS) ISSN 1091-6490, 109 (34). pp. 13549-13554. ISSN 1091-6490
Tran, JC, Zamdborg, L, Ahlf, DR, Lee, JE, Catherman, AD, Durbin, KR, Tipton, JD, Vellaichamy, A, Kellie, JF, LI, M, Wu, C, Sweet, Steve, Early, BP, Siuti, N, Leduc, R.D, Compton, P.D, Thomas, PM and Lelleher, N.L (2011) Mapping intact protein isoforms in discovery mode using top-down proteomics. Nature, 480 (7376). pp. 254-258. ISSN 00280836
Martinez-Garcia, Eva, Popovic, Relja, Min, Dong-Joon, Sweet, Steve M M, Thomas, Paul M, Zamdborg, Leonid, Heffner, Aaron, Will, Christine, Lamy, Laurence, Staudt, Louis M, Levens, David L, Kelleher , Neil L and Licht, Jonathan D (2011) The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells. Blood, 117 (1). pp. 211-220. ISSN 0006-4971
Sweet, Steve, Li, M, Thomas, PM, Durbin, K.R. and Kelleher, N.L (2010) Kinetics of re-establishing H3K79 methylation marks in global human chromatin. Journal of Biological Chemistry, 285 (43). pp. 32778-32786. ISSN 00219258
Cunningham, D.L, Sweet, Steve, Cooper, H.J and Hearth , J.K (2010) Differential phosphoproteomics of FGF signalling: identification of Src family kinase-mediated phosphorylation events. Journal of Proteome Research, 9 (5). pp. 2317-2328. ISSN 15353893
Sweet, Steve, Jones, AW, Cunningham, DL, Heath, JK, Creese, AJ and Cooper, HJ (2009) Database search strategies for proteomic data sets generated by electron capture dissociation mass spectrometry. Journal of Proteome Research, 8 (12). p. 5475. ISSN 15353893
Sweet, Steve, Bailey, C.M, Cunningham, D.L., Heath, J.K and Cooper, H.J. (2009) Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry. Molecular and Cellular Proteomics, 8 (5). pp. 904-912. ISSN 15359476
Sweet, Steve and Cooper, HJ (2007) Electron capture dissociation in the analysis of protein phosphorylation. Expert Review of Proteomics, 4 (2). pp. 149-159. ISSN 14789450
Sweet, Steve, Creese, A.J and Cooper, H.J (2006) Strategy for the identification of sites of phosphorylation in proteins: neutral loss triggered electron capture dissociation. Analytical Chemistry, 78 (21). pp. 7563-7569. ISSN 00032700